All mechanisms of clinical antibiotic resistance benefit from activities of polyspecific efflux pumps acting to reduce intracellular accumulation of toxins and antibiotics. In Gram-negative bacteria, the major polyspecific efflux transporters belong to the Resistance-Nodulation-cell Division (RND) superfamily of proteins, which are capable of expelling thousands of structurally diverse compounds. Recent structural and functional advances generated novel insights into mechanisms underlying the biochemical versatility of RND transporters. This opinion article reviews these mechanisms and discusses implications of the polyspecificity of RND transporters for bacterial survival and for the development of efflux pump inhibitors effective in clinics.

临床抗生素耐药性的所有机制都受益于多特异性外排泵的活动，以减少毒素和抗生素的细胞内积累。在革兰氏阴性细菌中，主要的多特异性外排转运蛋白属于抗性结瘤细胞分裂 (RND) 蛋白质超家族，能够排出数千种结构不同的化合物。最近的结构和功能进步对 RND 转运蛋白的生化多功能性的潜在机制产生了新的见解。这篇观点文章回顾了这些机制，并讨论了 RND 转运蛋白的多特异性对细菌存活和临床有效外排泵抑制剂开发的影响。